The invention relates generally to a pre-filled package containing a unit dose of medical gas and a method of making same. The invention is further directed to a method of introducing a unit dose for a gas into a patient using the prefilled syringe.
Gas-filled syringes are useful for a number of applications such as surgical procedures involving the injection of a gas bubble into a patient""s body. For example, a retinal tear can be treated using an intraocular surgical procedure during which a gas such as sulfur hexafluoride (SF6) or perfluoropropane (C3F8) is injected into the eye for gas tamponage. Carbon dioxide (CO2) gas can be injected into a blood vessel to facilitate percutaneous angioscopy. Nitric oxide (NO) gas and NO-releasing compounds can also be used to treat a number of medical conditions. For example, NO and NO-releasing compounds can be used for treatment of male impotence, inhibition of DNA synthesis and mitochondrial respiration in tumor cells, and relaxation of vascular smooth muscle for control of hypertension.
Gases used for surgery are often expensive and not available for purchase in ready-to-use form. Currently, gases for surgical procedures are purchased in a pressurized tank. Syringes are filled directly from the tank using a filling line. When a syringe is disconnected from the filling line, the gas in the filling line is released into the atmosphere. Thus, this method of preparing syringes for surgery is disadvantageous because a significant amount of gas is wasted. Due to the busy environment of a hospital, shut-off valves on gas tanks are frequently left open accidentally, causing an even greater amount of gas to be wasted than when gas syringes are being filled.
In addition to the problem of wasting expensive gases, a more serious clinical problem associated with filling syringes from gas tanks is dilution of the gas in the syringe prior to surgery. Syringes are sometimes prepared on the morning of the day they are to be used in surgery. The syringes are then placed in the operating room with other surgical devices until they are needed, which can be several hours later. Experiments have shown that leakage of gas from a syringe over a relatively short period of time can cause clinically significant dilution of the gas dose and therefore increase the risk of surgical complications. For instance, the concentration of sulfur hexafluoride in a plastic syringe has been observed to decrease from 97% at 30 seconds after aspiration to 76% at 60 minutes and 2% at 18 hours past aspiration.
The present invention overcomes the above-described disadvantages associated with known methods for preparing gas-filled syringes, while also realizing a number of advantages. In accordance with one aspect of the invention, a unit dose, gas-filled syringe is provided which is filled with gas and packaged in a gas barrier material prior to use to increase shelf-life, that is, minimize gas leakage and dilution of the contents of the syringe. The syringe is initially filled with a selected gas and sealed inside a container made from a high gas barrier material. The container is then also filled with the selected gas. The container material is selected to have a gas transmission rate sufficient to prevent the selected gas from diffusing out of the container into the atmosphere and to prevent atmospheric gas contaminants from entering the container. The gas is a pharmaceutically acceptable gas for injecting into the body of an animal. The gas is substantially free of oxygen and air and is at least 70% pure, and preferably 97% pure by volume.
In accordance with another aspect of the present invention, a method of packaging a gas-filled syringe is provided which comprises the steps of forming a container from a gas barrier material to enclose the syringe, placing the gas-filled syringe in the container, filling the container with the same gas as in the pre-filled gas syringe, and sealing the container to retain the gas and the syringe therein.
In accordance with yet another aspect of the present invention, a method of packaging a gas-filled syringe is provided which comprises the steps of forming a container from a gas barrier material to enclose the syringe, the container comprising a valve, placing the gas-filled syringe in the container, sealing the container to retain the syringe therein, evacuating the sealed container, and filling the container with the same gas as in the syringe using the valve.
In accordance with still yet another aspect of the present invention, a method of preparing a gas-filled syringe is provided which comprises the step of filling a container with a predetermined volume of a selected gas via an opening therein. The container is formed from a high gas barrier material to prevent gas from escaping from the container once the opening is sealed. The method further comprises the step of puncturing the container with the syringe needle and drawing the gas into the syringe by retracting the syringe-plunger.
A further aspect of the invention is basically attained by providing a method of introducing a gas into the eye during eye surgery, the method comprising the steps of providing a clean and sterile prefilled syringe containing a unit dose of a pharmaceutically acceptable gas and being substantially free of air and oxygen, the syringe having a syringe barrel, a gas delivery outlet, and a plunger. The syringe is completely enclosed in a substantially gas impermeable container, and the container has an internal volume surrounding the syringe filled with the pharmaceutically acceptable gas at a pressure at least substantially equal to atmospheric pressure. The syringe is removed from the container, and the gas delivery outlet is introduced into the eye of a patient and the gas is introduced into the eye.